Montelukast, is the International Non-proprietary Name (INN) of 1-[[[(1R)-1-[3-[(1E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(1-hydroxy-1-methylethyl)phenyl]propyl]sulfanyl]methyl]cyclopropaneacetic acid, and CAS No. 158966-92-8. Montelukast sodium salt (CAS No 151767-02-1) is currently used in treatment of asthma, inflammation, angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis and allograft rejection.
The structure of Montelukast sodium salt corresponds to formula (I):

Different synthetic strategies for the preparation of Montelukast and its salts are known. For instance, EP 480.717 discloses certain substituted quinolone compounds including Montelukast sodium salt, methods for their preparation, and pharmaceutical compositions using these compounds. Several preparation processes of Montelukast sodium salt are reported in this document. Example 161 relates to the preparation of Montelukast sodium salt. According to this Example, preparation of Montelukast sodium salt proceeds through its corresponding methyl ester, whose preparation comprises sodium hydride or cesium carbonate assisted coupling of methyl-1-(mercaptomethyl)-cyclopropaneacetate with the protected mesylate (2-(2-(2-(3(S)-(3-(2-(7-chloro-2-quinolinyl)-ethenyl)phenyl)-3-(methanesulfonyloxy)propyl)phenyl)-2-propoxy)tetrahydropyran, generated in situ. The methyl ester thus obtained is hydrolyzed to the Montelukast acid which is then converted directly to the sodium salt. This process is not particularly suitable for large scale production because it requires tedious chromatographic purification of the methyl ester intermediate and/or the final product, and yields of intermediates and final product are low. Other methods for the preparation of Montelukast and its salts have been described (cf. WO 04/108.679, US 2005/107612, WO 05/105751, WO 05/105749, WO 05/105750, CN 1428335, and CN 1420113).
Generally, Montelukast and its pharmaceutically acceptable salts are obtained by complex synthetic procedures which cause the formation of several by-products due to competing side reactions. These processes need tedious workups to isolate the Montelukast and its intermediates and thus results in excess time cycle, which in turn rendering the process more costly and less eco friendly. It is known that the purification of Montelukast is laborious and complex, being difficult to achieve a Montelukast with a high degree of purity since Montelukast and its precursors are unstable to oxygen and light causing a fast degradation. For the above reasons, Montelukast is generally obtained with a low degree of chemical and optical purity.
Some processes for the purification of Montelukast have been described in the art which are based on the formation of its salts. Thus, EP 737.186 relates to a process for the preparation of Montelukast or its salts, which comprises reacting the dilithium dianion of 1-(mercaptomethyl)-cyclopropane-acetic acid with the corresponding mesylate alcohol ((2-(2-(2-(3(S)-(3-(2-(7-chloro-2-quinolinyl)-ethenyl)phenyl)-3-(methanesulfonyloxy)-propyl)phenyl)-2-propanol), to obtain Montelukast. The crude acid is purified through the formation of its dicyclohexyl amine salt. Depending on the solvent used two crystalline forms of the salts can be obtained, so seeding plays a very critical role during crystallization. Patent application US 2005/234241 also describes a process for the preparation of Montelukast which occurs via the formation of organic Montelukast base salts. In particular, Examples 2 describe the formation of the tert-butylamine salt of Montelukast. Patent application WO 06/008751 also describes a process for the preparation of Montelukast and a process for its purification via the formation of several organic Montelukast base salts.
According to WO 05/074935, Montelukast sodium can be purified by obtaining Montelukast free acid as a solid and converting the Montelukast free acid into Montelukast sodium.
Therefore, from what is known in the art it is derived that the provision of a purification process of Montelukast, and its pharmaceutical acceptable salts which proceeds with high yield and high optical purity, is interesting for the industrial manufacture of these compounds.